Approximately one million plateletpheresis procedures are performed each year in the U.S., including 3,500 in the Platelet Center of the Department of Transfusion Medicine, NIH. Healthy donors are eligible to undergo plateletpheresis and leukapheresis procedures as often as 24 times per year. During plateletpheresis, citrate anticoagulant is added to the blood collection pathway to prevent clotting in the apheresis device, and is infused into the donor during the procedure. Adverse effects related to citrate administration are common, and include acute hypocalcemia due to the formation of calcium-citrate complexes. Recent studies in our Department indicate that changes in serum calcium, parathormone, osteocalcin, alkaline phosphatase, and vitamin D levels are also present and may be sustained for up to 24 hours after apheresis. In addition to volunteer plateletpheresis donors, the NIH Department of Transfusion Medicine maintains a registry of approximately 500 leukapheresis donors, who provide components for in vitro research use. These research apheresis procedures may involve processing twice as much blood volume (10 liters) as is processed in a typical plateletpheresis procedure (5 liters). Thus during leukapheresis, the total dose of citrate administered to the donor may be twice as great as that which occurs during plateletpheresis. Leukocyte and plateletpheresis donors may undergo more than 100 apheresis procedures during the course of their participation in the donor program at NIH. Donors are encouraged to take oral calcium carbonate supplements before or during apheresis if citrate related symptoms occur or have occurred in the past. The impact of serial, frequent, long-term apheresis donations on total body calcium balance and bone density is unknown. In this study, we will compare bone density measurements, as assessed by DEXA scans of the wrist, lumbosacral spine, hip and entire body in three cohorts of donors (1) 75 long-term plateletpheresis donors who have undergone at least 50 plateletpheresis procedures at NIH in the past 10 years, (2) 75 long-term research leukapheresis donors who have undergone at least 50 leukapheresis procedures at NIH in the past 10 years, and (3)150 age, gender, and race matched whole blood donors, who have never undergone apheresis, as a control group. Comprehensive laboratory evaluations of the effect of citrate administration on bone metabolism and body calcium and magnesium metabolism before and after apheresis will be performed. The effect of prophylactic oral and intravenous calcium administration on apheresis-induced changes in these laboratory parameters will be assessed. This information will have a major impact on our understanding of the short and long-term adverse effects of citrate administration in committed apheresis donors, and may also provide insight into calcium, magnesium, and phosphorus metabolism.